The long-term goal of this project continues to be the study of the plasma lipoproteins in an effort to determine how the levels of these lipoproteins are regulated. During the past year, we have continued our efforts to characterize the subunit proteins of the rat lipoproteins. We have shown that the apo-HDL consists of three major proteins with molecular weights of 27,000, 35,000 and 46,000 in addition to the 8-12,000 molecular weight "C" proteins. One of these larger molecular weight proteins is the homologue of the human A-1 protein; another is a protein high in arginine; and the third, is as yet uncharacterized. The proteins have been separated by SDS gel electrophoresis, but we have also found isoelectric focusing a useful tool in separating subunit proteins and characterizing them. We have found that the subunit composition of the various lipoproteins can be altered. Thus, in cholesterol-fed rats the VLDL and the intermediate density lipoprotein (1.006-1.03) which appears, contains certain of the subunits found in HDL, including the A-1 and the high arginine protein. The HDL is markedly diminished, but in addition, demonstrates the absence of the high arginine protein, as well as selective loss of certain of the "C" proteins. In the rat made diabetic by the administration of streptozotocin, marked hyperlipoproteinemia occurs. Most striking are the changes in the C-11 and C-111 proteins present in the HDL and VLDL. Coincident with these changes, is the finding that serum from these rats inhibits lipoprotein lipase activity, suggesting a possible mechanism for the production of the hyperlipoproteinemia that occurs in these rats.